Basic-alimentary tractColitis is associated with thymic destruction attenuating CD4+25+ regulatory T cells in the periphery☆
Section snippets
Mice
The tgε26 recipient mice, derived from (C57BL/6 × CBA) F1 (H2Kk/b) mice, were maintained as previously described.10 (C57BL/6 × CBA) F1 mice were purchased from Jackson Laboratory (Bar Harbor, ME). C57BL/6 TCR transgenic HY-Rag−/− mice were purchased from Taconic Laboratory (Germantown, NY). For all experiments involving HY-Rag−/− mice, only female mice were used. C57BL/6 TCR transgenic F5-RAG−/− (F5) mice were generously provided by Dr. C. Levelt (MIT, Cambridge, MA).11 Signal transducer and
TR cells develop in bone marrow transplanted neonatal tgε26 mice
To examine whether a temporal window existed, during which wt hematopoietic cells did reconstitute the tgε26 thymus, 2- to 8-day-old tgε26 neonates were transplanted with bone marrow from wt (C57BL/6 × CBA) F1 mice. The resultant BM→tgε26neo mice developed a thymus that had a normal distribution of CD4, CD8, TCR-αβ, and CD3 positive cells (Table 1). In the spleen and lymph nodes of the mice, mature T cells were detected at levels 70% to 100% of wt controls in the peripheral lymphoid organs (
Discussion
This study shows that when a neonatal tgε26 mouse receives BM, TR cells develop, protecting the mouse from colitis. Conversely, in BM→tgε26adult mice, few TR cells can be detected. The neonatal tgε26 thymus is therefore similar to the Rag−/− thymus in that both support development of TR cells. Unlike the Rag−/− thymus, the adult tgε26 thymus lacks keratin 8+5− cortical thymic epithelial cells (TECs).7, 18 High-affinity interaction between developing thymocytes and MHC class II expressing
Acknowledgements
The authors thank Dr. D. Podolsky, D. Howie, and M. Morra for a critical review of the manuscript and M. Comiskey for technical support.
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Cited by (0)
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Supported by grants from the National Institutes of Health (DK52510 to C.T.; DK47677 to A.K.B.; DK43351 to C.T. and A.K.B.) and the Crohn’s and Colitis Foundation of America (to Y.P.D. and S.J.S.).
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W.A.F. and Y.P.D. contributed equally to this paper.